[The in vitro effect of alpha-2 agonists on thrombocyte function and density of thrombocyte alpha-2 receptors]

alpha 2-Agonists are being used increasingly in anaesthesia and intensive care medicine because of their antihypertensive, analgesic and sedative properties. Platelets bear alpha 2-receptors on the cell surface. Stimulation of these receptors by agonists induces platelet aggregation. The present study examined whether in vitro incubation of blood with the alpha 2-agonists clonidine and dexmedetomidine decreases alpha 2-receptor density and hereby influences platelet aggregation.

Whole blood of 20 healthy volunteers was incubated over 24 h at 37 degrees C with 1 ng/ml clonidine or 1 or 10 ng/ml dexmedetomidine. Induced platelet aggregation was determined by means of turbidometry. Epinephrine (22 mumol/l) or collagen (20 mg/l) served as inductors. The density of alpha 2-receptors was measured in radioligand assays with 3H-Yohimbine. Phentolamine was used to assess unspecific binding. The data were analyzed with an analysis of variance.

Neither 1 ng/ml clonidine nor 1 ng/ml dexmedetomidine altered platelet aggregation or alpha 2-receptor density in comparison with the control sample. As a major result we found that 10 ng/ml dexmedetomidine caused a significant (P < 0.05) reduction in epinephrine-induced platelet aggregation (16.0 +/- 5.4%, n = 20, mean +/- SEM) compared with the control (46.0 +/- 1.3%, n = 20). alpha 2-Receptor density was not any different from the control.

This in vitro study showed that clinically relevant concentrations of 1 ng/ml clonidine or dexmedetomidine did not alter platelet aggregation or alpha 2-receptor density, even after 24 h exposure. However, 10 ng/ml dexmedetomidine was found to diminish significantly epinephrine-induced platelet aggregation, but did not change alpha 2-receptor density. This result showed that desensitization of platelet aggregation can occur without quantitative changes in alpha 2-receptors.